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Aim To study the influence of SiniSan on the Tryptophankynurenine (TRPKYN) pathway, the activity and content of the key metabolism enzyme indoleamine2, 3dioxygenase (IDO).Methods The mice model was established by intraperitoneal injection LPS (1 mg · kg1).Using ELISA to detect the contents of IFNγ in serum.The content of Tryptophan and kynurenine in brain tissue were detected by using HPLCMS/MS technique.The mRNA expression level of IDO in brain tissue was detected by using realtime PCR.Results 4 hours after the LPS injection, the immobility time of model group mice prolonged.The content of IFNγ in serum increased significantly(P < 0.05).Meanwhile, the activity of IDO in brain tissue and the mRNA expression level of IDO increased.SiniSan could short the immobility time of mice, reduced the content of IFNγin serum (P < 0.05).It could also inhibit the activity of IDO and the expression of mRNA (P < 0.01).Conclusion SiniSan blocks the pathway of IDO activation, inhibit the activity of IDO and reduce the content of it.SiniSan produces antidepressant effect by adjusting the TRPKYN metabolism.